Frontiers in nutritionJul 23, 2026

Microbial metabolites linking gut-brain communication and neurodevelopmental disorders

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jul 24, 2026

Abstract

Disruptions in microbial metabolites are associated with neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD).

Microbial metabolites play a crucial role in connecting gut health to brain function.
Evidence suggests reduced production of short-chain fatty acids (SCFAs) and altered kynurenine pathway metabolites in individuals with neurodevelopmental disorders.
Increased levels of neurotoxic compounds like para-cresol (p-cresol) have been reported in association with these disorders.
The metabolite-producing microbiome is influenced by maternal factors, nutrition, and environmental exposures during early life.
New intervention strategies, including probiotics and metabolite-based therapies, are proposed to target microbial metabolites for improving child neurodevelopment.

Simplified

The microbiota-gut-brain axis (MGBA) has emerged as a critical regulator of neurodevelopment, with microbial metabolites serving as key signaling molecules that bridge the intestinal ecosystem and the central nervous system. This review gathers current evidence that connects disruptions in microbial metabolites to the pathogenesis of neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Our comprehensive overview discusses major neuroactive metabolite classes-short-chain fatty acids (SCFAs), tryptophan derivatives, bile acids, and phenolic compounds-and their established roles functions in affecting neuroinflammation, epigenetic programming, synaptic function, and blood-brain barrier integrity. Converging evidence from human multi-omics studies and preclinical models frequently reported patterns of metabolic dysregulation in NDDs, including reduced SCFA production, altered kynurenine pathway metabolites, and accumulation of neurotoxic compounds such as para-cresol (p-cresol). However, substantial heterogeneity exists across studies, and causal evidence in humans remains predominantly associative. We further examine the critical early-life window during which the metabolite-producing microbiome is shaped by maternal factors, nutrition, and environmental exposures, with lasting consequences for neurodevelopmental trajectories. Finally, we discuss new intervention strategies such as probiotics, dietary substrates, fecal microbiota transplantation, and metabolite-based therapies, and propose a plan to transition from associative findings to causal, personalized approaches using microbial metabolites as biomarkers and therapeutic targets in child neurodevelopment.